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RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function
RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decr...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664964/ https://www.ncbi.nlm.nih.gov/pubmed/26619789 http://dx.doi.org/10.1038/srep17383 |
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author | Wang, Han-Ying Hsieh, Pei-Fen Huang, De-Fong Chin, Pey-Shyuan Chou, Chih-Hsuan Tung, Chun-Che Chen, Shin-Yuan Lee, Li-Jen Gau, Susan Shur-Fen Huang, Hsien-Sung |
author_facet | Wang, Han-Ying Hsieh, Pei-Fen Huang, De-Fong Chin, Pey-Shyuan Chou, Chih-Hsuan Tung, Chun-Che Chen, Shin-Yuan Lee, Li-Jen Gau, Susan Shur-Fen Huang, Hsien-Sung |
author_sort | Wang, Han-Ying |
collection | PubMed |
description | RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders. |
format | Online Article Text |
id | pubmed-4664964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46649642015-12-03 RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function Wang, Han-Ying Hsieh, Pei-Fen Huang, De-Fong Chin, Pey-Shyuan Chou, Chih-Hsuan Tung, Chun-Che Chen, Shin-Yuan Lee, Li-Jen Gau, Susan Shur-Fen Huang, Hsien-Sung Sci Rep Article RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders. Nature Publishing Group 2015-12-01 /pmc/articles/PMC4664964/ /pubmed/26619789 http://dx.doi.org/10.1038/srep17383 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wang, Han-Ying Hsieh, Pei-Fen Huang, De-Fong Chin, Pey-Shyuan Chou, Chih-Hsuan Tung, Chun-Che Chen, Shin-Yuan Lee, Li-Jen Gau, Susan Shur-Fen Huang, Hsien-Sung RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function |
title | RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function |
title_full | RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function |
title_fullStr | RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function |
title_full_unstemmed | RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function |
title_short | RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function |
title_sort | rbfox3/neun is required for hippocampal circuit balance and function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664964/ https://www.ncbi.nlm.nih.gov/pubmed/26619789 http://dx.doi.org/10.1038/srep17383 |
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